title: Novel mutations in SPG11 cause hereditary spastic paraplegia associated with early-onset levodopa-responsive Parkinsonism.
abstract: BACKGROUND
  Autosomal recessive hereditary spastic paraplegia with thin corpus callosum is a neurodegenerative disorder characterized by spastic paraparesis, cognitive impairment, and peripheral neuropathy. The neuroradiologic hallmarks are thin corpus callosum and periventricular white matter changes. Mutations in the SPG11 gene have been identified to be a major cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and recently also proven to be responsible for juvenile parkinsonism associated with spastic paraplegia.
  
  
  METHODS
  We describe one Italian autosomal recessive hereditary spastic paraplegia with thin corpus callosum patient who unusually presented at onset, 16 years, with parkinsonism-like features, responsive to dopaminergic therapy. Then the clinical picture evolved and became more complex. A brain magnetic resonance imaging scan showed thin corpus callosum and hyperintense T(2)-weighted lesions in periventricular regions, and the (123)I-ioflupane single-photon emission coupled tomography was abnormal.
  
  
  RESULTS
  Genetic analysis detected two novel mutations, a c.3664insT variant in compound heterozygosity with a c.6331insG mutation, in SPG11.
  
  
  CONCLUSIONS
  This case confirms the high genetic and clinical heterogeneity associated with SPG11 mutations. It also offers further evidence that parkinsonism may initiate autosomal recessive hereditary spastic paraplegia with thin corpus callosum and that parkinsonian symptoms can have variable dopaminergic response in these patients.
authors.affiliation: Department of Neurology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Guidubaldi
authors.forename: Carla
authors.initials: C
authors.lastname: Piano
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: Gabriella
authors.initials: G
authors.lastname: Silvestri
authors.forename: Martina
authors.initials: M
authors.lastname: Petracca
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessa
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bentivoglio
mesh_terms: D000328:Adult; D000978:Antiparkinson Agents / Q000627:therapeutic use; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000209:etiology* / Q000235:genetics*
chemical_list: D000978:Antiparkinson Agents; D011506:Proteins; C520412:SPG11 protein, human; D007980:Levodopa